Phase I Study of Nicotinamide for Early Onset Preeclampsia

This is a Phase I study of vitamin B3-amide (nicotinamide) dietary supplementation in pregnant women with early onset preeclampsia. The investigators will enroll 10 pregnant women at 24-32 weeks' gestation with the diagnosis of preeclampsia. If the woman is anticipated to remain undelivered for 48 hours after diagnosis she will receive vitamin B3-amide, 500 mg/day given in the morning (n=5) or 1000 mg given in the morning (n=5), continuing until delivery or for 14 days, whichever occurs first. Maternal blood will be collected at baseline and twice a day on days 1, 3, and 7 of nicotinamide administration to measure nicotinamide metabolites, The objectives of this Phase I study are to to test safety of nicotinamide.

Study Overview

• Status: Completed
• Conditions: Hypertension; Pregnancy Induced Hypertension; Superimposed Preeclampsia
• Intervention / Treatment: Drug: Nicotinamide 500 mg; Drug: Nicotinamide 1000 mg

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7516
      • University of North Carolina Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Maternal age 18-45 years
2. Informed written consent

3. Preeclampsia or new onset hypertension between 24-32 completed weeks' gestation

   1. Hypertensive complications of pregnancy defined as new onset systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg on two occasions 6 hours apart; OR > 300 mg proteinuria on 24 hour urine collection OR urine P/C ratio >0.3;
   2. Dating criteria based on menstrual dating confirmed by first or second trimester ultrasound OR second trimester ultrasound if menstrual dating unavailable;
   3. Deemed clinically stable by primary clinician and candidate for expectant management (delayed delivery);
4. Maternal liver function tests < 3x ULN
5. Maternal platelet count > 100,000 mm3
6. Fetal well-being established by estimated fetal weight > 5th %tile; normal amniotic fluid volume (MVP > 2 cm); normal Umbilical Artery Dopplers; AND reactive NST(non-stress test) or BPP (biophysical profile) > 6
7. Plan for expectant management until delivery
8. Delivery not anticipated within first 48 hours

Exclusion Criteria:

1. Preeclampsia < 24 or > 33 weeks' gestation;
2. Suspected fetal structural or chromosomal abnormality;
3. Pre-existing renal disease (creatinine > 1.5 mg/dL)
4. Pre-existing vascular disease (systemic lupus; cardiac disease;)
5. Plan for delivery within 48 hours
6. Any pre-existing medical condition that would increase risk for liver toxicity (e.g. hepatitis B or C; HIV)
7. Evidence of cerebral dysfunction (seizures; cerebral edema on CT/MRI; headache unresolved with oral analgesics)
8. Pulmonary edema
9. HELLP (hemolysis, elevated liver enzymes, low platelets syndrome)
10. Evidence of liver dysfunction (LFTs > 3x ULN)
11. Thrombocytopenia (platelets < 100,000 mm3)
12. Evidence of fetal compromise: EFW(estimated fetal weight) < 5th percentile; BPP < 6; absent or reverse diastolic UA blood flow; oligohydramnios (MVP < 2 cm)
13. Placental abruption defined as unexplained vaginal bleeding
14. Preterm labor defined as regular contractions and cervical change
15. Any condition deemed by the investigator to be a risk to mother or fetus in completion of the study
16. Any condition deemed by the investigator to require delivery within 48 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotinamide 500 mg; Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.	Drug: Nicotinamide 500 mg; Nicotinamide 500 mg taken by mouth each morning; Other Names: Vitamin B3 amide
Experimental: Nicotinamide 1000 mg; Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.	Drug: Nicotinamide 1000 mg; Nicotinamide 1000 mg taken by mouth each morning; Other Names: Vitamin B3 amide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Specific adverse events were Maternal liver toxicity, defined as > 3x ULN of ALT(Alanine amniotransferase) or AST (Aspartate amniotransferase), maternal report of side effects, and fetal adverse effects.	Within 48 hours of dosing

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: North Carolina Translational and Clinical Sciences Institute
• Investigators: Principal Investigator: Kim A Boggess, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): December 3, 2015
• Study Completion (Actual): December 3, 2015

Study Registration Dates

• First Submitted: August 7, 2014
• First Submitted That Met QC Criteria: August 8, 2014
• First Posted (Estimate): August 11, 2014

Study Record Updates

• Last Update Posted (Actual): November 2, 2018
• Last Update Submitted That Met QC Criteria: March 15, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: preeclampsia; nicotinamide; pregnancy-induced hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 13-2203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No